The objective of the proposed experiments is to provide a basic biochemical explanation for the acceleration of the rate of deoxyhemoglobin S polymerization inside the intact erythrocyte when compared to isolated hemoglobin S solutions which has been observed in this laboratory. Transverse water proton relaxation rates will be used to measure the rate of deoxyhemoglobin S polymerization. Intact erythrocyte membranes will be isolated and the comparison of polymerization rates made using right-side-out and inverted membranes. It is suspected that hemoglobin binding sites located on the inside of the erythrocyte membrane serve as a template for the polymerization process. By comparing the effect of the inside and the outside of the erythrocyte membrane it will be possible to determine whether the accelerated rate of polymerization observed in intact erythrocytes is specific or a general membrane phenomenon. In addition, we propose to investigate whether the decrease in plasma concentration of cholesterol esters observed in this laboratory in children with sickle cell anemia is a consequence of this particular disease state, or whether it is a general condition related to hemolytic anemia.